8-羟基鸟嘌呤核苷酸酶抑制剂TH588诱导人肺腺癌细胞凋亡研究  

Apoptosis of human lung adenocarcinoma cells induced by 8-oxoguanine nucleoside triphosphatase inhibitor TH588

作　　者：庞金龙 李姗姗 黄富豪 伍宇 张语涵 李娴 蒋琛琛 刘浩 PANG Jin-long;LI Shan-shan;HUANG Fu-hao;WU Yu;ZHANG Yu-han;LI Xian;JIANG Chen-chen;LIU Hao(School of Pharmacy,Bengbu Medical College,Bengbu 233030,Anhui Province,China)

机构地区：[1]蚌埠医学院药学院,安徽蚌埠233030

出　　处：《中国临床药理学杂志》2021年第4期412-415,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81372899);安徽省教育厅高校优秀青年人才支持计划基金资助项目(gxyq2019037);蚌埠医学院研究生科研创新计划基金资助项目(Byycx1962);补益类中药炮制共性技术研究及大健康产品开发基金资助项目(2019-BYHX-03)。

摘　　要：目的探讨8-羟基鸟嘌呤核苷酸酶(8-oxoguanine nucleoside triphosphatase,MTH1)抑制剂TH588对肺腺癌细胞A549和H1975凋亡的影响。方法将细胞分为空白组(正常培养的肺腺癌细胞)和低、中、高剂量实验组(8,16,32μmol·L-1 TH588处理肺腺癌细胞)。使用细胞计数试剂盒-8(Cell Counting Kit-8,CCK-8)检测TH588对肺腺癌细胞A549和H1975增殖的影响。Transwell检测TH588对肺腺癌细胞A549和H1975的迁移能力的影响。AnixinⅤ-FITC/PI双染法检测TH588对肺腺癌细胞凋亡的影响。Western Blot检测TH588对肺腺癌细胞凋亡相关蛋白B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)的影响。结果 TH588处理24 h后,A549和H1975细胞低、中、高剂量实验组存活率分别为(76.15±1.02)%,(70.63±4.16)%,(57.42±2.15)%;(78.05±2.06)%,(62.86±3.45)%,(58.47±2.70)%。TH588处理48 h后,A549和H1975低、中、高剂量实验组存活率分别为(62.26±3.84)%,(45.19±1.08)%,(36.03±2.95)%;(73.21±1.84)%,(57.96±3.18)%,(32.47±10.19)%。TH588处理72 h后,A549和H1975细胞低、中、高剂量实验组存活率分别为(59.16±1.15)%,(35.63±2.26)%,(28.56±3.60)%;(63.08±0.98)%,(50.27±2.15)%,(25.76±11.06)%。A549和H1975细胞对照组及低、中、高剂量实验组的相对迁移率分别为(100.00±2.15)%,(80.50±2.07)%,(65.25±3.83)%,(36.76±2.25)%;(100.00±4.05)%,(85.65±2.79)%,(72.48±2.96)%,(43.05±1.98)%。A549和H1975细胞对照组及低、中、高剂量实验组的凋亡率分别为(8.25±0.57)%,(23.17±3.40)%,(42.50±4.83)%,(49.02±8.15)%;(4.05±1.20)%,(6.46±1.85)%,(7.55±1.05)%,(14.87±4.46)%。A549和H1975细胞对照组及低、中、高剂量实验组Bcl-2/Bax值分别为1.18±0.01, 0.75±0.03, 0.68±0.03, 0.52±0.04;1.28±0.04, 1.05±0.04, 0.54±0.04,0.45±0.03。A549和H1975细胞低剂量组、中剂量组、高剂量组的细胞存活率、相对迁移率、凋亡率及Bcl-2/Bax值与对照组比较,差异有统计学意义(P<0.05)。结论 TH588显著促进了肺腺癌细胞A549和H1975的凋亡,其机�Objective To investigate the effect of TH588, an 8-oxoguanine nucleoside triphosphatase(MTH1) inhibitor, on apoptosis of lung adenocarcinoma cells A549 and H1975.Methods Cells were divided into blank group(normal cultured lung adenocarcinoma cells)and low,medium and high-dose experimental group(8,16,32 μmol · L-1 TH588 treated lung adenocarcinoma cells).Cell Counting Kit-8(CCK-8) was used to detect the effect of TH588 on the proliferation of lung adenocarcinoma cells A549 and H1975.Transwell assay was used to examine the effect of TH588 on the migration ability of lung adenocarcinoma cells A549 and H1975.The effect of TH588 on apoptosis of lung adenocarcinoma cells was detected by Anixin V-FITC/PI double staining.Western Blot was used to detect the effect of TH588 on apoptosis-related proteins B lymphocytoma-2(Bcl-2) and Bcl-2-related X protein(Bax) in lung adenocarcinoma.Results After 24 h of TH588 treatment,the survival rates of A549 and H1975 cells in the low,medium and high-dose experimental groups were(76.15 ± 1.02) %,(70.63 ± 4.16) %,(57.42 ± 2.15) %;(78.05 ± 2.06) %,(62.86 ± 3.45) %,(58.47 ± 2.70) %,respectively.After 48 h of TH588 treatment,the survival rates of the low,medium and high-dose experimental groups of A549 and H1975 were(62.26 ± 3.84) %,(45.19 ± 1.08) %,(36.03 ± 2.95) %;(73.21 ± 1.84) %,(57.96 ± 3.18) %,(32.47 ± 10.19) %,respectively.After 72 h of TH588 treatment,the survival rates of A549 and H1975 cells in the low,medium and high-dose experimental groups were(59.16 ± 1.15) %,(35.63 ± 2.26) %,(28.56 ± 3.60) %;(63.08 ± 0.98) %,(50.27 ± 2.15) %,(25.76 ± 11.06) %,respectively.The relative migration rates of A549 and H1975 cell control group and low,medium and high-dose experimental groups were(100.00 ± 2.15) %,(80.50 ± 2.07) %,(65.25 ± 3.83) %,(36.76 ± 2.25) %;(100.00 ± 4.05) %,(85.65 ± 2.79) %,(72.48 ± 2.96) %,(43.05 ± 1.98) %,respectively.The apoptotic rates of A549 and H1975 cells in the control group and the low,medium and high-dose experimental groups were(8.25 �

关 键 词：肺腺癌 8-羟基鸟嘌呤核苷酸酶 TH588 凋亡 

分 类 号：R97[医药卫生—药品]